PB1895: ANALYSIS REVEALS CANCER-ASSOCIATED GENE MUTATIONS IN CHRONIC MYELOID LEUKEMIA PATIENTS ：A CHINESE MONOCENTRIC RETROSPECTIVE STUDY
Authors: J. Huang, S. Wang, X. Xu
Journal: HemaSphere (2022)

Background: Recent genetic studies have shown that tyrosine kinase inhibitors (TKI) resistant or intolerant Chronic myeloid leukemia (CML) patients often carry one or more genetic changes related to myeloid malignancies, suggesting that additional mutations other than ABL1 mutation may lead to TKI treatment failure or disease progression. Aims: We performed sequencing of 22 CML patients using next-generation sequencing (NGS). 23 CML patients tested WT1 expression detection. Methods: The second cohort (No. 1) tested by second-generation sequencing included 22 CML patients. The second cohort (No. 2) tested by WT1 expression detection included 23 CML patients. The study has been approved by the institutional ethics committee and patients provided written informed consent in accordance with the Fourth Affiliated Hospital of Zhejiang University School of Medicine.Definitions Response was defined as BCR-ABL1 transcript levels according to the International Scale (IS) ≤10%, ≤1% and ≤0.1% at 3, 6 and 12 months after initiating TKI-therapy. Molecular response with 4.0 log reduction (MR4.0) was defined as 0.01%. Molecular response with 4.5 log reduction (MR4.5) was defined as 0.0032% or less BCR-ABLtranscript level. The comparison between groups of measurement data showed that the data with normal distribution were analyzed by one-way ANOVA or t-test. Results: Overall, a total of 51 mutations involving 25 genes were detected most frequently in the ASXL1 (40.9%), KMT2C (27.3%), DIS3 (18.2%), ATM (13.6%), DNMT3A (13.6%) and NOTCH3 (13.6%) genes. NOTCH3 and RELN mutations were only 3/20 (10%) in those who did not reach 12M-MMR group. Although the difference was not statistically significant (P = 0.214, P = 0.476). The number of median mutant genes in reaching MR4.5 group was 1 (0-3). The number of median mutant genes in not reaching MR4.5 group was 4 (0-6), and the difference was statistically significant (P = 0.033). ASXL1 mutation in reaching MR4.0 group and non reaching MR4.0 group was statistically significant (P = 0.023). With KMT2C mutation group had lower PFS (P = 0.079). There was a potential statistical difference between low WT1 expression group and high WT1 expression group in early EMR after a 3-month treatment (P = 0.089).The research was supported by the Key R&D Program of Zhejiang, No. 2022C03137; Public Technology Application Research Program of Zhejiang, China, No. LGF21H080003; the Key Project of Jinhua Science and Technology Plan, China, No. 2020-3-011; the 2019–2024 Academician Workstation of the Fourth Affiliated Hospi-tal of the Zhejiang University School of Medicine; the 2019–2022 Key Medical Dis-cipline (Hematology) Fund of Jinhua, China. *Correspondence to: Dr Jian Huang, Department of Hematology, The Fourth Affiliated Hospital of Zhejiang University School of Medicine. N1 Shangcheng Road. Yiwu, Zhejiang, Peoples R China.E-mail: [email protected] Image:Summary/Conclusion: Genomic risk assessment can improve the risk stratification of clinical diagnosis, and can more accurately identify patients with poor effect of TKI treatment in the era of TKI treatment. The treatment effect of CML patients with NOTCH3, RELN and ASXL1 mutations and more than two gene mutations is poor. CML patients with high expression of WT1 at diagnosis have poor therapeutic effect in the early stage.